Could automated template based quantification of benzodiazepine receptors in brain single photon emission tomography with 123I NNC 13-8241 be used to demonstrate neuronal damage in traumatic brain injury?

Automated methods are required for the analysis of brain single photon emission tomography images. We applied an automated method to assess the benzodiazepine receptor distribution in the brain. Images of 19 patients with mild traumatic brain injury who had received I NNC 13-8241 were compared with a mean brain template accumulated from 18 healthy volunteers. To obtain more information, we calculated the neuronal benzodiazepine receptor binding in the brain by using pre-defined anatomical regions and a voxel-by-voxel technique. The group of patients with mild traumatic brain injury differed significantly (P =0.015) from the group of healthy volunteers in the distribution of benzodiazepine receptors. This methodological work suggests that a reference based template and a three-dimensional brain model help in regional analysis and quantification and could be useful in demonstrating permanent neuronal damage after head injury.

[123I]beta-CIT SPECT demonstrates decreased brain dopamine and serotonin transporter levels in untreated parkinsonian patients.

Striatal dopamine transporters (DATs) and serotonin transporters (SERTs) were evaluated in untreated patients with Parkinson's disease (PD) and controls using single-photon emission computed tomography (SPECT) with 2beta-carboxymethoxy-3beta-(4-iodophenyl)tropane ([123I]beta-CIT). The striatal DAT specific to non-displaceable uptake ratios of 29, and the SERT uptake measurements of 27, PD patients were compared with those of 21 and 16 controls, respectively. The results were correlated with Unified Parkinson's Disease Rating Scale (UPDRS) scores, the Hoehn & Yahr stage, age, duration of the disease, and the major PD signs. The specific DAT binding in the caudate, the putamen and the caudate/putamen ratio were measured. In all of the PD patients the striatal uptake values were bilaterally reduced, being 36.9% (P < 0.001) lower than those of the controls. In the hemiparkinsonian patients the reduction was greater on the side contralateral to the initial symptoms (33.3% vs. 27.8%) and the uptake ratios indicated a more pronounced deficit in the putamen (39.1%) than in the caudate (27.9%). The DAT uptake correlated with the UPDRS total score and activities of daily living (ADL) and motor subscores, the Hoehn & Yahr stage, and rigidity score. PD patients had significantly higher caudate to putamen ratios than the controls. In the PD patients the SERT values were lower in the thalamic and frontal regions. The SERT uptake ratio of the frontal area correlated with the UPDRS subscore I. [123I]beta-CIT SPECT provides a useful method for confirming the clinical diagnosis of PD with correlation to disease severity. Additionally, this technique allows the simultaneous measurement of SERT uptake and shows that PD patients, interestingly, seem to have decreased SERT availability in the thalamic and frontal areas.

Brain single photon emission computed tomography at term age for predicting cerebral palsy after preterm birth.

In order to assess the predictive value of neonatal brain perfusion with single photon emission computed tomography (SPET) with regard to neuromotor outcome at a corrected age of 18 months, 34 infants with birth weight <1,500 g and gestation age <34 weeks underwent brain technetium-99m ethylcysteinate dimer (99Tc(m)-ECD) SPET at term age. The perfusion defects were estimated by visual interpretation. Consecutive semiquantitative assessment was made in 26 cases and reference values for the tracer were collected from images of 17 preterm infants with normal outcome after the follow-up period. Relative regional cortical (frontal, sensorimotor, parietal and occipital), cerebellar and thalamic perfusion levels were evaluated in middle sagittal slices and hemispheric asymmetries in transaxial slices. Perfusion defects predicted cerebral palsy (CP) (n = 11) with 82% sensitivity, 70% specificity and 74% accuracy, the corresponding figures for ultrasound (US) being 73, 83 and 79%, respectively. The sensitivity of SPET in predicting moderate or severe CP (n = 7) was 100% and the specificity 67%, the corresponding figures for US being 71% and 74%, respectively. Brain SPET seems to identify the most severe forms of CP in preterm infants very well at term age, but cannot identify all mild ones. In addition to a low specificity, the radiation exposure restricts usefulness of the method for clinical purposes.

Elevated hypothalamic/midbrain serotonin (monoamine) transporter availability in depressive drug-naive children and adolescents.

Cumulative data suggest depression in adulthood being connected to reduced availability of brain serotonin while the role of dopamine remains less specific. Prospective studies have shown a continuity of depressive episodes from childhood to adulthood, combined with poor social function and excess mortality. The object of this study was to examine whether alterations in brain serotonin and/or dopamine transporter levels are already present in depressive children and adolescents. We examined 41 drug-naive patients (aged 7-17) by single photon emission tomography (SPET) using iodine-123-labelled 23-carbomethoxy-3P3(iodophenyl) tropane [123I]beta-CIT as a tracer for monoamine transporters. In addition to the ordinary clinical examination, the patients were given a structured interview and information was gathered from teachers and parents with questionnaires. The diagnoses were established by consensus evaluation between three child psychiatrists. To test the serotonin hypothesis and the dopamine hypothesis regarding depression in children and adolescents, the series was divided into groups with depression present (31) and no depression present (10). In this study, the depressive child and adolescent patients had significantly higher serotonin transporter availability (P < 0.02) in the hypothalamic/midbrain area. Age did not correlate to the hypothalamic/midbrain serotonin transporter binding ratio. No significant difference in dopamine transporter availability in striatum was found between the depressive and the nondepressive children and adolescents.

Dopamine transporters increase in human brain after alcohol withdrawal.

Dopaminergic transmission has been suggested to be a main mechanism mediating reinforcement, withdrawal and craving associated with alcohol addiction. We measured here striatal dopamine (DA) transporter binding from 27 alcoholics within 4 days after cessation of prolonged heavy drinking and after a 4-week period of abstinence with single photon emission computed tomography (SPECT) using a cocaine analogue, iodine-123-beta-CIT. Controls were 29 healthy volunteers. Blind quantitative analyses of the SPECT data revealed markedly lower DA transporter binding in alcoholics on admission for detoxification than in the non-alcoholic controls. After a 4-week period of abstinence DA transporter binding increased significantly in the alcoholics (P<0.0001) reaching the levels of the healthy controls. The most substantial recovery in DA transporter binding occurred during the first 4 days of abstinence. The data indicate that prolonged heavy drinking decreases DA transporter binding and disturbs synaptic dopamine transport. This may sensitize alcoholics to dopaminergic transmission, which may lead to early relapse after ethanol withdrawal.

Silicone replacement arthroplasty for Kienböck's disease.

Thirty-nine patients with Kienböck's disease underwent silicone replacement arthroplasty between 1979 and 1994. The patients were followed-up from 1 to 18 years (mean, 8 years). Sixteen prostheses (41%) have had to be removed, from 1 to 18 years postoperatively (mean, 5.6 years), 15 of them because of pain and silicone synovitis or cysts. It appears that silicone synovitis with cyst formation is an inevitable problem in the wrist after silicone replacement arthroplasty of the lunate, and this procedure is only a temporary solution for Kienböck's disease.

Brain perfusion after treatment of childhood acute lymphoblastic leukemia.

UNLABELLED: Children with acute lymphoblastic leukemia (ALL) have impairment in their neuropsychological functioning and morphological changes in their brain after cranial irradiation and chemotherapy. The aim of this study was to identify possible brain perfusion defects caused by different types of treatment and their association with abnormalities in cerebral MRI and neuropsychological and clinical neurological findings. METHODS: Twenty-five consecutive children with ALL at the cessation of chemotherapy or after 1 yr were included. All of the children were given intravenous and intrathecal methotrexate for central nervous system therapy, 13 of them received cranial radiation therapy. Brain SPECT, cerebral MRI, clinical neurological and neuropsychological evaluations were performed. RESULTS: Eleven of the 25 patients (44%) had brain perfusion defects in SPECT, eight of whom were treated with chemotherapy alone, and three received cranial irradiation. Two patients had small bilateral white matter changes on MRI; their brain SPECT scans were abnormal, although the findings were not related. Impairment of neuropsychological functioning was found in 86% of the patients tested. No significant difference between the patients with abnormal and normal SPECT were found. Those patients with abnormal SPECT were younger than those with normal SPECT and had received more frequent intravenous methotrexate infusions. CONCLUSION: Brain SPECT detected perfusion defects that had occurred after treatment for childhood ALL. These defects may be related to frequent administration of a combination of intravenous and intrathecal methotrexate and/or young age.

No difference in cardiac innervation of diabetic patients with painful and asymptomatic coronary artery disease.

OBJECTIVE: To test the hypothesis that diabetic autonomic neuropathy interfering with sensory impulses from the heart by sympathetic denervation is the major cause of the high prevalence of asymptomatic coronary artery disease (CAD) in diabetic patients. RESEARCH DESIGN AND METHODS: We evaluated cardiac sympathetic innervation in a population-based group of 10 asymptomatic diabetic patients with angiographically proven CAD and in an age- and sex-matched group of 10 diabetic patients with symptomatic CAD using [123I]metaiodobenzylguanide (MIBG) scintigraphy. Exercise electrocardiography and myocardial perfusion imaging by 201Tl were used to detect myocardial ischemia, and standard cardiovascular tests were used to diagnose autonomic nervous dysfunction. RESULTS: Thallium scintigraphy revealed perfusion defects in all 10 symptomatic patients and in 9 of the asymptomatic patients. MIBG accumulation defects were found in all cases with painless and with painful disease. In the asymptomatic group, the denervation area exceeded the ischemic area in six cases and areas with total MIBG accumulation defects were seen in four cases. In one case, the MIBG defect was not in the ischemic region. In the symptomatic group, the denervation area exceeded the area of the ischemic region in all cases and areas of total denervation were seen in six cases. The autonomic nervous function tests were abnormal in two asymptomatic and three symptomatic patients with CAD. CONCLUSIONS: Cardiac sympathetic denervation is common in both patients with painful CAD and patients with asymptomatic CAD regardless of diabetic autonomic neuropathy. This finding supports the view that sympathetic innervation of the heart is highly sensitive to ischemia and this profound effect of ischemia masks the potential effects of autonomic neuropathy on sympathetic innervation. Mechanisms leading to the lack of ischemic pain in diabetic patients with CAD are complex and are not solely explained by autonomic neuropathy.

Detection of cervical metastases of thyroid medullary carcinoma by MoAb anti-CEA scintigraphy and immunohistochemistry.

Four patients with medullary thyroid carcinoma (MTC) were examined using anti-carcinoembryonic antigen (CEA) scintigraphy. Two patients had positive and two normal scintigraphic findings, although all the patients had elevated blood test markers (calcitonin or CEA). One patient with clinical suspicion of MTC metastases had only a faintly positive anti-CEA image, although single-photon emission tomographic scanning was used to increase the sensitivity and resolution of the method. Therefore, digital image processing of the planar images was performed to obtain more detailed information. The analysis revealed distinct accumulation of the activity at the right side of the neck at 20 h post administration. The specificity of the antibody binding in the malignant cells was confirmed after surgery by immunohistochemical staining of the tumour specimens for CEA. Both conventional and confocal laser scanning microscopy revealed distinct positive staining, indicating that the results obtained from the anti-CEA scanning showed specific binding of the labelled antibody in the neoplastic tissue.

Assessment of tissue viability in frostbite by 99Tcm-HDP scintigraphy: an experimental study in New Zealand white rabbits.

Since the appearance of superficial tissue is often an unreliable indicator of deep tissue viability in cases of frostbite, radionuclide scintigraphy with 99Tcm-disodium oxidronate (HDP) was used to assess changes in tissue viability after experimental freezing and thawing of the rabbit ear. One shaved ear, left or right, of each of eight New Zealand white rabbits was frozen with a glass bottle (diameter of bottom 2 cm) filled with liquid nitrogen (-180 degrees C) for 5 min under Ketalar-Rompun anesthesia, the other ear serving as a control. Radionuclide scintigraphy was performed by giving a bolus intravenous injection of 130-170 MBq (3.5-4.5 mCi) 99Tcm-HDP. Radionuclide imaging was used to follow the development of the demarcation line. Scintigraphy was performed 2 h after frostbite and then after 24 h, 48 h, 1 week and 3 weeks. The frostbitten area seemed macroscopically to be warm and swollen immediately after the induction of frostbite. Scintigraphy showed the frostbitten area to be much warmer than the surrounding tissue for the first week and it was not until after that the first cold spots appeared in the middle of the frostbitten area. The necrotic and vital tissue could easily be distinguished after 3 weeks.

Effect of perivascular sympathectomy on distal blood flow in the rabbit forepaw. A dynamic isotope experiment with Tc99m.

Perivascular sympathectomy, used for treating patients suffering from vasospastic disorders of the hand, is believed to cause an increase in the distal blood flow. Its effects were examined here by performing the operation on the metacarpal arteries of the left forepaw of ten New Zealand White rabbits, the right forepaw serving as a control. Blood flow was measured by Tc99m radionuclide angiography five days before the operation and three days and two and a half weeks after it. There was no statistically significant postoperative increase in blood flow in the distal parts, so that it may be concluded that at least in this experimental model, the distal sympathectomy did not have any such effect.

Isometric exercise testing and echocardiography at rest in aortic valve incompetence.

Thirty patients with aortic valve incompetence and 21 control subjects were examined by M-mode echocardiography at rest and radionuclide ventriculography during submaximal handgrip exercise. The patients had greater left ventricular dimensions and end-systolic wall stress values but peak systolic wall stress values did not differ. During exercise the controls' ejection fraction increased by 3 +/- 4%, 95% confidence interval (CI) from +1% to +5%, while the aortic incompetence patients showed no change -1% +/- 5%, CI from -3 to +1%. The 15 symptomatic aortic incompetence patients had a different ejection fraction response from the controls (-2 +/- 4%, p less than 0.01), CI from 4% to +1%, but the 15 asymptomatic patients had not (0 +/- 6%, not significant, CI from -3% to +3%). Three symptomatic and two asymptomatic patients with a decrease in ejection fraction below 5% during handgrip were not identified by left ventricular size and function of systolic loading conditions at rest. Neither echocardiographic or radionuclide parameters of left ventricular size and function at rest correlated with the individual ejection fraction changes during handgrip. Thus, in aortic valve incompetence, the radionuclide angiography assessed functional response to handgrip cannot be predicted by left ventricular size and function or systolic loading conditions at rest.

Radiolabelling of monoclonal antibodies: optimization of conjugation of DTPA to F(ab')2-fragments and a novel measurement of the degree of conjugation using Eu(III)-labelling.

F(ab')2 fragments (at concentrations of 5-30 mg/ml) derived from monoclonal antibodies raised against human prostate specific acid phosphatase were derivatized with a bicyclic anhydride of diethylenetriaminepentaacetic acid (cDTPAA) in the molar ratios of cDTPAA/F(ab')2 of 1:1, 5:1, 10:1 or 50:1. The most optimal product, aimed at radioimaging of prostatic cancer was obtained when the antibody fragment concentration was at least 10 mg/ml and the molar ratio of cDTPAA to F(ab')2 was 5:1. cDTPAA was added dissolved in dimethylsulfoxide (DMSO). Under these conditions, 1.8-2.2 DTPA molecules/F(ab')2 molecule were bound, giving a coupling efficiency of 37%-44%, and the labelling efficiency with 111In (3 mCi/1 mg protein) was 95% +/- 3% (n = 7). The antibody fragment completely retained its immunoreactivity measured by radioimmunoassay and showed no aggregation when studied using sodium dodecyl sulfatepolyacrylamide gel electrophoresis (SDS-PAGE). For evaluation of the degree of conjugation of DTPA to the antibody fragment, a novel technique was developed relying on the use of EuCl3, and the measurement of europium fluorescence employing time resolved fluorometry. Results by EuCl3 labelling were identical to those obtained by the conventional 111InCl3 labelling method.

Left ventricular dimensions during isometric exercise in aortic valve incompetence assessed by M-mode echocardiography and gated equilibrium radionuclide angiography.

We compared M-mode echocardiographic and gated equilibrium radionuclide angiography assessment of the left ventricular (LV) dimensions at rest and during isometric exercise in 18 patients with chronic aortic valve incompetence. The two methods showed a satisfactory correlation when comparing LV size at rest and during exercise (LV end-diastolic dimension in echocardiography vs LV end-diastolic volume in radionuclide angiography, r = 0.80, P less than 0.01 at rest and r = 0.81, P less than 0.01 at rest and r = 0.75; P less than 0.01 during exercise), but fractional shortening in echocardiography and ejection fraction in radionuclide angiography did not correlate (r = 0.27, not significant (NS) at rest and r = 0.34, NS during exercise). Thus echocardiography and radionuclide angiography describe LV dimensions at rest and during handgrip exercise in a similar fashion, documenting the concordance of these noninvasive methods to describe LV size in aortic incompetence at rest and during exercise.

A low-dose CT-pelvimetry.

The suitability of CT for pelvimetry was studied. For accurate measurement of the true conjugate and interspinous diameter, a lateral topogram and an axial CT slice were taken. The radiation dose was reduced from 1 mGy (in conventional system) to 0.1-0.2 mGy.

Radiation gonad doses received by children in intravenous urography and micturition cysto-urethrography.

Measurements of gonad doses in intravenous urography (IVU) was performed on 47 children and in micturition cysto-urethrography (MCU) on 57 children. Ionization chamber dosimeters were placed rectally in girls and fixed on the scrotum in boys. Gonad dose ranged from 27 mrad to 201 mrad in girls and from 7 mrad to 112 mrad in boys during IVU; during MCU doses ranged from 53 mrad to 1900 mrad in girls and form 24 mrad to 309 mrad in boys. Risk of leukemia and genetic risk were calculated.